Department of Health and Human Services
Part 1. Overview Information

 

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title

Mechanisms of Cancer Drug Resistance and Sensitivity (U54)

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-CA-17-009

Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.395, 93.394 

Funding Opportunity Purpose

The goal of this Funding Opportunity Announcement (FOA) is to create a network of Drug Resistance and Sensitivity Centers (DRSCs) to develop innovative strategies to study mechanisms of tumor resistance or sensitivity to anticancer therapy.  It is hoped that such studies will permit future efforts to identify and exploit these phenomena in clinical settings.

Each funded DRSC will become a member of the Drug Resistance and Sensitivity Network.  Each DRSC may include multiple members and capabilities at the same or different institution that are necessary to fulfill the need for highly specialized multidisciplinary expertise.  There may be multiple linked projects within each DSRC that will be under the overall authority of a Program Director/Principal Investigator (PD/PI).  Applications involving several investigators from single or multiple institutions working together on a promising area of cancer resistance or sensitivity to drug therapy are encouraged.

The outputs from the DRSCs are expected to inform the development of novel strategies for precision medicine clinical trials (beyond the scope of this FOA) that can overcome drug resistance and sensitivity to anti-cancer agents.

Key Dates

 

Posted Date

December 8, 2016

Open Date (Earliest Submission Date)

February 3, 2017

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

March 3, 2017, by 5:00 PM local time of applicant organization. All types of applications allowed for this funding opportunity announcement are due on this date.

No late applications will be accepted for this Funding Opportunity Announcement.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

May-June, 2017

Advisory Council Review

August 2017

Earliest Start Date

September 2017

Expiration Date

March 4, 2017

Due Dates for E.O. 12372

Not Applicable

** ELECTRONIC APPLICATION SUBMISSION REQUIRED**

NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Purpose

The goal of this Funding Opportunity Announcement (FOA) is to create a network of Drug Resistance and Sensitivity Centers (DRSCs). These DRSCs will be expected to conduct preclinical research focused on innovative strategies to understand and combat mechanisms of tumor resistance (intrinsic or acquired) and/or to exploit tumor sensitivity to anti-cancer therapies. These strategies should explore genetic and other molecular characteristics of the cancer underlying sensitivity/resistance to anticancer treatments.

Each DRSC should be based on 2-3 interrelated research projects. DRSC applicants may propose collaborative arrangements (within one institution and/or with partnering institutions) to ensure all capabilities that might be necessary to fulfill the need for highly specialized multidisciplinary expertise.

The proposed projects should have a clear translational potential to inspire and aid the development of novel therapeutic strategies based on mechanistic understanding of resistance and/or sensitivity to anticancer drugs or drug combinations.  It is also intended that each of the specialized centers to be supported will pursue a distinct area of cancer drug sensitivity and/or resistance research. 

Collectively, the DRSCs will act as a network to serve as a critical preclinical part to NCI’s clinical drug development. Preclinical discoveries resulting from research performed by DRSCs should enable future clinical application of concepts to prevent and/or overcome cancer drug resistance within the NCI Cancer Therapy Evaluation Program (CTEP) clinical trials networks.  (However, actually conducting such a clinical trial is beyond the scope of this FOA.)  This effort is a part of the NCI contribution to the Precision Medicine initiative (https://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-medicine-initiative).

Background

Drug resistance has been a recognized problem in cancer treatment for decades.  Recent progress in biomedical research has enhanced our understanding of the pathways and mechanisms that confer resistance to anticancer drugs.  Similarly, there have been advances in animal models and patient-derived models used to predict the potential clinical benefit from suppression of particular resistance pathways.   Many mechanisms of resistance to targeted anti-cancer agents exist, including modification of the intended drug target, and induction of adaptive, or bypass signaling pathways.  Studies of suppression of cell death pathways by anti-apoptotic proteins and their modulation by pharmacologic agents have led to the development of several drugs with clinical activity.  In addition, recent studies have demonstrated in some models the critical importance of chromatin remodeling and epigenetic modulation of cancer drug resistance.  Recent studies have also demonstrated examples of synthetic sensitivity and/or lethality in numerous signaling and metabolic pathways in cancer cells, with particular application to the genetic defect in DNA repair and DNA damage response pathways.  Many human cancers have a high incidence of mutations or alteration in copy number in DNA repair or DNA damage response genes. 

This recent progress makes it possible to build upon promising strategies to identify mechanisms of drug sensitivity and/or overcome mechanisms of cancer drug resistance in the clinic.  The NCI hopes that the insights from work funded by this FOA will provide novel agents for the NCI's Investigational New Drug (IND) portfolio, or provide drug combinations or strategies to delay resistance to the existing agents.  CTEP, through collaborations with pharmaceutical companies, has developed a portfolio of approximately sixty-five anti-cancer agents.  These agents include a wide variety of signal transduction inhibitors, monoclonal antibodies impacting cancer cell growth and survival, anti-tubulins, apoptosis-modulating agents, epigenetic-modulating agents, immunotherapy agents, and other drugs modulating tumor angiogenesis and hypoxia. 

 
Main Requirements for Drug Resistance and Sensitivity Centers

Research Focus. The proposed DRSC should focus on new experimental models and diagnostic techniques and use human tumor samples whenever possible. Applicants should attempt an iterative approach between "bench and bedside" to develop understanding of the ramifications of the proposed mechanisms of cancer drug sensitivity and resistance.  Research proposed should be aimed at answering important questions in clinical cancer drug resistance/sensitivity such as whether strategies can be developed to test for drugs or drug combinations effective in stopping the appearance of resistance by the mechanism under study.  Research proposed should also incorporate studies to demonstrate how quickly after treatment with anti-cancer therapy evidence of their mechanism of drug resistance might be observed and whether evidence of their proposed mechanism might be monitored by tumor biopsies or sequential blood assays. 

Funding preferences may be given to applications involving an in-depth exploration of druggable targets and/or resistance mechanisms amenable to inhibition with CTEP portfolio agents (or to drugs that modulate the same pathway as CTEP agents); however, applications proposing other drugs or targets are permitted.

Scope of Research Projects

The research efforts for each proposed Center must be based on two or three well developed and interrelated research projects. All of the proposed projects must have a primary focus on the area of drug resistance/sensitivity and should meet the following characteristics. 

  • Preliminary Data. The projects are expected to be supported by preliminary data obtained using in vivo models and/or human samples from clinical trials to develop a strategy that either will select patients most likely to respond or will develop treatment options that could overcome a mechanism of resistance. 
  • Required in vivo Studies. Drug resistance projects should aim at development of a mechanistic understanding of the resistance mechanism under study and include in vivo studies demonstrating that the currently available agents might prevent resistance or re-sensitize resistant tumor cells in this setting.
  • Studies on Druggable Target. A substantial part of research proposed (a project or, at least, one distinct Specific Aim of a project) should be devoted to cancer drug resistance with a druggable target relevant to human cancer.
  • Responsive Types of Therapeutic Agents. Studies of resistance and/or sensitivity to agents targeting signaling pathways, including hormonal agents, are within the scope of this FOA.  Investigation of the mechanism of drug sensitivity and/or drug resistance utilizing patient samples from clinical trials involving, e.g., agents targeting DNA repair or DNA damage response, apoptosis, cell cycle regulation or epigenetic DNA modification, as well as studies examining resistance to DNA damaging agents and immunotherapeutic agents, are also within the FOA scope.  Studies of resistance to ionizing radiation are not within the FOA scope.

Possible Directions of Drug Resistance Studies

Examples of drug resistance studies appropriate for this FOA include, but are not limited to the following aspects:

  • Intrinsic cancer drug resistance;
  • Acquired/adaptive resistance to chemotherapy agents or to other agents which may involve a specific target similar or identical to that of a CTEP IND agent, although other drugs and targets are permitted (provided that such studies include assessing of pharmacologic inhibition of the target;
  • Resistance to a targeted agent in combination with a standard-of-care anticancer agent or chemotherapy combination;
  • Acquired/adaptive resistance to targeted cancer agents with activation of alternative signaling pathways, particularly if those adaptive resistance pathways can be inhibited by CTEP IND agents;
  • Resistance to antibodies that block tumor growth or survival signaling pathways;
  • Resistance to hormonal agents;
  • Suppression of cell death pathways by anti-apoptotic protein activation/overexpression;
  • Resistance to DNA damaging cytotoxic agents;
  • Epigenetic modulation of drug resistance;
  • Resistance to immune checkpoint inhibitors and other immunomodulatory agents;
  • Proteo-genomic analysis of cancer cell responses to therapy, with global analyses of changes in RNA and protein expression, as well as genome-wide copy number variation and mutations after drug therapy, as long as the ultimate goal is the identification of druggable targets to modulate drug resistance; 
  • Network analysis of biomolecules highly correlated with tumor growth following treatment to define adaptive response pathways;  
  • Dynamic monitoring of clonal evolution and treatment response using serial sampling to assess, as appropriate, cell-free DNA (cfDNA), circulating tumor cells, RNA-containing exosomes, and/or other relevant molecular characteristics; and/or
  • Systems biology approaches integrating various data types obtained from pre- and post-treatment biopsies of patient-derived xenograft (PDX) models or human tumors.  Approaches might include mathematical, statistical, or computational methods for predicting drug resistance and/or perturbation due to drug therapy. 

Possible Directions of Drug Sensitivity Studies

Examples of drug sensitivity studies appropriate for this FOA include, but are not limited to, the following aspects.

  • Clinical bio-specimens acquired before and possibly after treatment with investigational agents in appropriate preclinical models to pursue observations of synthetic sensitivity/lethality from results of cancer selection screens;
  • Studies involving agents targeting DNA repair or DNA damage response pathways, which are complementary to other DNA repair pathways lost in particular cancers;
  • Tumor genetic losses leading to dependency on druggable compensatory proteins, such as the sensitivity to mTORC1 inhibition by everolimus in bladder cancers with TSC1/2 loss; and/or
  • Developing agents targeting regulation of gene expression critical to a specific phenotype or cancer cell state, such as the super-enhancer network regulated by the MYC oncogene.

Non-responsive Studies

The following types of studies are beyond the scope of the FOA:

  • Resistance/sensitivity to ionizing radiation;
  • Basic cancer biology research that is unrelated to mechanistic understanding of cancer drug resistance or sensitivity;
  • Studies proposing a clinical trial.

Applications proposing such studies will be viewed as non-responsive and will not be reviewed.

Expected Team Capabilities of Individual DRSCs

Applicants' teams are expected to have appropriate transdisciplinary scope of expertise and capabilities. Specific needs may vary but, in general, are anticipated to cover appropriate preclinical models for cancer drug resistance, such as conditionally-reprogrammed cell lines, organoid cultures, and/or patient-derived xenograft models for in vivo studies of anticancer agents.  The team should also have demonstrated ability to conduct pharmacodynamic and pharmacokinetic studies in animal models to demonstrate inhibition of cancer targets in vivo at tolerable drug concentrations that might be translated to clinical trials.  The ability to validate drug resistance/sensitivity targets (by a combination of appropriate pharmacodynamic and pharmacokinetic studies with systems biology and/or bioinformatics analyses) will also be important for ensuring translational applicability of DRSC studies.

The Coordination of the Drug Resistance and Sensitivity Network

The NCI Drug Resistance and Sensitivity Center Steering Committee (DRSC-SC) will coordinate DRSN activities with the goal of maximizing the optimal utilization of resources.  The DRSC-SC will promote, in collaboration with other NCI program staff members, the exchange of scientific findings and potential collaborations between the investigator teams and NCI laboratories, as well as potential interactions between the investigators and members of NCI’s Early Phase Clinical Trial networks. For details, see Section VI.2. under Cooperative Agreement Terms Conditions of the Award.

NCI Resources to Support the Drug Resistance and Sensitivity Network

NCI will assist the DRSC investigators by providing various additional resources.  For example, NCI will provide investigational agents in its IND agents portfolio for preclinical studies via a Material Transfer Agreement (MTA).  NCI investigators at the Frederick National Laboratory for Cancer Research (FNLCR) may have available for study PDX models of relevant histology and genotype.  In some cases, patient bio-specimens acquired before and/or after drug treatment in NCI clinical trials may be available for study.  Biomarker assay procedures developed by the Pharmacodynamic Assay Development & Implementation Section (PADIS) laboratories within the NCI Division of Cancer Treatment and Diagnosis (DCTD) may be of use as well.  The DRSC-SC will facilitate entry of genomic and relevant clinical data from the project sites into the Genomic Data Commons repository in order to share and extend molecular findings with databases and analytic tools within the GDC.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The NCI intends to fund up to five awards corresponding to a total set-aside of $6.25 M (total costs) in FY2017.

Award Budget

Application budgets must not exceed $750,000 per year in direct costs.

Award Project Period

The total project period may not exceed 5 years.  

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Governments

  • State Governments
  • County Governments
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

Given the potential for multi-disciplinary and multi-institutional teams, applicants are encouraged to take advantage of the multiple PDs/PIs option.

An individual may be designated as a PD/PI only on one DRSC application.  

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility
Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct and involve distinct research teams (i.e., are led by different PDs/PIs and have non-overlapping other key persons).

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
Section IV. Application and Submission Information
1. Requesting an Application Package

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

William C. Timmer, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6130
Email: william.timmer@nih.gov

Page Limitations

Component Types Available in ASSIST

Research Strategy/Program Plan Page Limits

Overall

12

Admin Core (Use for Administrative Core)

 6

Project (Use for Research Projects)

12 (each project)

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

  • Overall: required
  • Administrative Core: required
  • Research Projects: 2 required, maximum 3 allowed
Overall Component

When preparing your application in ASSIST, use Component Type ‘Overall’.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement  (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Facilities and Resources: In addition to standard items, describe the intellectual environments (e.g., academic or other research) of the research team members and how this milieu may inspire creativity and facilitate achieving the goals of the proposed DRSC.

Project/Performance Site Location(s) (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research & Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.  

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Specific Aims:  Outline the overall goals for the proposed Drug Resistance and Sensitivity Center (DSRC) and its scientific focus.   

Research Strategy:   Provide an overview of the proposed DRSC.  Address all the specific aspects indicated below using the sub-sections as defined:

Sub-section A. Significance: Describe the impact of successful completion of the proposed work, both in regards to understanding of cancer biology and in regards to the potential for translation of the work to improve therapy for cancer patients.

Subsection B. DSRC Framework: Describe the overarching organizational framework and vision of the proposed DRSC, its scientific focus, strengths, and leadership in the research field.

Sub-section C. Research Teams: Summarize the major collective strength of the research team in the proposed area of research. Without repeating information from individual biosketches, explain how the specific expertise of team members (e.g., cancer biology, in vitro and in vivo studies, molecular genomics, computational biology, bioinformatics, etc.) will be used to advance the proposed research program.

Sub-section D.  Individual Research Projects: Summarize the proposed research projects, their importance and interrelationship, and the rationale for their inclusions.  The research projects should be proposed based on one or more of the scientific areas outlined in Section I, Scope of Scientific Research.  It is expected that most responses to the FOA will have 2-3 related research projects studying different aspects of an area of cancer drug resistance or sensitivity in a coordinated manner.

Sub-section E. DRSC Integration: Describe how the DSRC and the investigational team will collectively support the overarching goal of the Center through multi-disciplinary and/or multi-institutional collaborations. In particular, if any collaboration proposed involves new interactions between research groups, discuss the means to be employed to foster collaboration and communication between the different components of the research team.   

Letters of Support: All Letters of Support relevant to the overall application should be provided u here. Include, for example, letters documenting institutional commitments to the proposed DRSC.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • Resource Sharing Plan should be provided only under the Overall component but it should cover all the activities proposed for the DSRC.
  • Data Sharing Plan is expected to adhere to the guidelines in the NCI Genomic Data Sharing Policy (https://www.cancer.gov/grants-training/grants-management/nci-policies/genomic-data).

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

PHS Assignment Request Form (Overall)

All instructions in the SF424 (R&R) Application Guide must be followed. 

Administrative Core

When preparing your application in ASSIST, use Component Type ‘Admin Core.’

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

  • Applicant Information
  • Type of Applicant (optional)
  • Descriptive Title of Applicant’s Project
  • Proposed Project Start/Ending Dates
PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)
  • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
  • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
  • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
  • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used. 
  • The contact PD/PI of the DSRC Research Center should serve as the Administrative Core Leader.
Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package.

PD/PI Effort Commitment. Any PD/PI (whether designated as contact or not) must commit a minimum of 1.2 person-months effort per year to the award.  This commitment cannot be reduced in later years of the award. Note that this is a minimum effort level that should be increased as appropriate to meet the needs of the work.

The budget should also include travel funds for the PD(s)/PI(s) and the leads from each research project to attend the annual NCI DRSC-Steering Committee meeting and participate in other network related activities.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administrative Core)

Specific Aims:  List the goals for the Administrative Core.  

Research Strategy:   Address the specific aspects indicated below using the sub-sections as defined:

Sub-section A. Core Structure: Outline the organization and function of the Administrative Core. Incorporate the plans for specific administrative activities of the DRSC including, but not limited to, progress reports, monthly meetings and teleconferences, development of a DRSC advisory group, travel for the PD(s)/PI(s) and team leaders to scientific meetings, and other activities.  Describe briefly the plans for coordination and communication with the DRSC and NCI scientific staff.

Sub-section B. Leadership and DRSC Organization: Outline the organization of the leadership structure and overall DRSC structure (provide respective organizational diagrams). Describe the lines of responsibilities, including, as applicable, the effort distribution across the participating institutions (i.e., institution submitting application and participating institutions on a sub-contractual basis).

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: Resource Sharing Plans should only be included in the Overall component of the application.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

PHS Inclusion Enrollment Report (Administrative Core)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.  

Research Projects

When preparing your application in ASSIST, use Component Type ‘Project’.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Project)

Complete only the following fields:

•   Applicant Information

•   Type of Applicant (optional)

•   Descriptive Title of Applicant’s Project (preceded with "Project 1:", or "Project 2:" or "Project 3:")

•   Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement  (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project/Performance Site Location(s) (Research Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Project)

  • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Leader’ and provide a valid eRA Commons ID in the Credential field;
  • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component;
  • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component;
  • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used. 

Budget (Research Project)

Budget forms appropriate for each individual research project should be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Project)

Specific Aims:  Describe the goals of the proposed Research Project and how the work proposed responds to the overall objectives of the FOA as described in Section I, Funding Opportunity Description.

Research Strategy: Describe the research strategy using the standard sub-sections of Research Strategy (Significance, Innovation, and Approach) defined in the SF424 Application Guide with additional guidance as defined below:

Under Significance sub-section:

In addition to other standard aspects address the following points.

  • When presenting the rationale and hypothesis for the study, define the important questions in clinical cancer drug resistance/sensitivity that your project will attempt to address;
  • Outline the translational significance of the proposed study. For example, explain how the proposed strategy can ultimately help select patients most likely to respond to a given type of treatment, or how getting mechanistic molecular insights related to druggable target can lead to new treatment option(s) that could overcome a mechanism of resistance;
  • Explain how a given project can contribute to the DRSC overarching goals and how it will integrate/interact with other project(s) proposed;
  • For anticancer agents proposed, identify clearly their IND status (indicating which agents are in the NCI-IND portfolio); and
  • Provide supporting preliminary data, preferably obtained with the agents proposed for studies.

Under Innovation sub-section:

In addition to other standard aspects address the following specific point.

  • List new/innovative models, diagnostic techniques, and other tools/approaches, that you have available and propose to use and/or plan to develop or improve during the project period.

Under Approach sub-section:

As parts of standard description, address the following points.

  • Adhering to guidelines and requirements defined for research focus and scientific scope in Section I of the FOA, describe how you propose to explore the aspects of the drug resistance and/or sensitivity defined by the Specific Aims of your project;
  • If applicable, consider to use and describe an iterative approach between "bench and bedside";         
  • Whenever appropriate for your specific project and feasible, indicate whether human tumor samples will be used (which is encouraged and preferred);
  • Provide sufficient details such as characteristics of preclinical models to be used, and/or human samples from clinical trials with the selected anticancer agent; and
  • Mark clearly the part(s) of research that focus on the required aspect of druggable target.

In addition, the Approach sub-section must include the following items under separate headings, as indicated below.

  • Under a heading "Rigor and Transparency":

- Describe how the experimental design and methods proposed will achieve robust and unbiased results; and

- Explain how relevant biological variables, such as sex, are factored into research designs and analyses for studies in vertebrate animals and humans.

  • Under a heading "Future Directions": 

- Describe the overall foresight of the DSRC (beyond the initial DSRC award) for advancing knowledge on the mechanisms of cancer sensitivity or resistance to anticancer agents in the area of a given research project; and

- Outline how the DSRC will be able to use the results from the proposed studies to develop strategies for novel, precision medicine clinical trials to overcome drug resistance or sensitivity (note that although new clinical trials are not part of this FOA the outcomes of DSRC research are expected to pave way for appropriate clinical trials in the future.)

Resource Sharing Plan:  Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. Resource Sharing Plans should only be included in the Overall component of the application.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. 

PHS Inclusion Enrollment Report (Research Project)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.  

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Section V. Application Review Information
1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this FOA, note the following:

Reviewers will provide an overall impact score for the entire Drug Resistance and Sensitivity Center (Overall component). In addition, assigned reviewers will provide individual "criterion scores" for the Overall criteria but not for the other components.  The Research Projects and Administrative Core will be evaluated, but each will receive only one overall adjectival (not numerical) rating.

Overall Impact - Overall

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the DRSC to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the DRSC proposed).

Scored Review Criteria - Overall

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a DRSC that by its nature is not innovative may be essential to advance a field.

Significance

Does the DRSC address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the DRSC are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? 

Specific for this FOA:  Are the organizational framework, vision, and scientific focus of the proposed DRSC designed to enable a unique understanding of drug resistance or sensitivity?  Is the requirement for the DRSC structure to accomplish the proposed goals of the program well-articulated? Are the DRSC components and the investigators team well integrated to collectively support the overarching goal of the Center and the vision of the Drug Resistance and Sensitivity program?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the DRSC? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific for this FOA: Are the backgrounds, expertise, and commitments of the PD(s)/PI(s) and other key persons sufficient for the proposed scope of activities and in line with the overall goals of the DRSC? For applications involving multiple PDs/PIs, are their designated roles and responsibilities well defined, adequate, and complementary for achieving the goals of the proposed Research Center? How well do the proposed collaborations between the DRSC PD(s)/PI(s) and other key persons integrate to achieve the overarching research goals?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? 

Specific for this FOA: Does the proposed DSRC involve biologically innovative concepts of drug resistance and/or sensitivity?  and/or methods to understand? Are the DRSC goals original and innovative in terms of basic understanding of cancer responses to therapeutic agents? Are the proposed concepts and approaches innovative within the context of related research such that the results could close current knowledge gaps and overcome barriers to drug resistance?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the DRSC? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?  Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the DRSC involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?   

Specific for this FOA: How well does the proposed DRSC take advantage of multidisciplinary approaches to promote and advance the understanding of the mechanisms of drug resistance and sensitivity? Are the overall research goals, experimental design, methods, and capabilities sound and well developed?  Are effective mechanisms in place to foster strong collaborative interactions and promote “cross-fertilization” among investigators and participating institutions?  Are mechanisms for facilitating sharing of samples and resources well planned or in place?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

Specific for this FOA:  Will the scientific environment at the participating institutions stimulate

trans-disciplinary research collaborations?

Additional Review Criteria - Overall

As applicable for the DRSC proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed DRSC involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed.  For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

 
Revisions

Not Applicable

Additional Review Considerations - Overall

As applicable for the DRSC proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .


Authentication of Key Biological and/or Chemical Resources

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Review Criteria - Research Projects

Reviewers will consider each of the review criteria outlined below to assess the scientific merit of the Research Projects but each project will receive only one overall adjectival impact rating (criterion scoring is not used for this component). A project does not need to be strong in all categories to have major scientific impact. For example, a Research Project that by its nature is not innovative may be essential to advance the field.

Significance

Does the proposed research project address an important problem related to cancer drug resistance and sensitivity? Is there a strong scientific premise for the project? If the aims and milestones of the project are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods in the field and on the management of the resistance mechanism being studied? 

Investigators

Are the investigators appropriately trained and well suited to carry out this work? Is the project proposed appropriate to the experience and expertise of the project leader and other researchers and team members?

Innovation

Does the proposed project employ novel concepts, approaches, and/or methods to solve the problem stated in the study? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies, theories, and/or technologies?

Approach

Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?  Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? Does the applicant acknowledge potential problem areas and consider alternatives, as appropriate?

Environment

Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments benefit from unique features of the scientific environment

or employ useful collaborative arrangements?

Additional Review Criteria-Research Projects

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Review Criteria - Administrative Core

Reviewers will provide only one overall adjectival impact rating for the Administrative Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

Is there adequate evidence for the managerial and collaborative capabilities of the proposed DRSC’s leadership? How appropriate is the leadership structure of the proposed DRSC in terms of facilitating: achievement of the overall goals of the DRSSC; integration of multiple institutions participating in a given project; and collaboration in cross-DRSC activities?

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the NCI in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.  NCI's programmatic goal is to develop a diverse network of DSRCs studying a variety of cancer drug resistance and sensitivity topics. Therefore, a programmatic priority will be to select applications that represent non-overlapping research areas. Multiple applications within the same specific area (e.g., DNA damage) will not be selected for funding. 
3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information
1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the following primary responsibilities:

  • Determine the DRSC's directions, coordinate research approaches and procedures, and oversee the analyses and interpretation of research data;
  • Oversee the timely release and sharing of specimens and data according to the approved plans;
  • Participate in the development and evaluation of cross-DRSC activities that will cross-test novel projects;
  • Participate in the annual DRSC Steering Committee meeting, and periodic conference calls organized by the DRSC Coordinating Center;
  • Cooperate with NCI Project Scientists in the program evaluation process;
  • Accept and implement all scientific and practical decisions approved by the DRSC Steering Committee to the extent consistent with applicable grant regulations;
  • Provide information to the NCI Program Directors concerning progress by submitting annual progress reports in a standard format;
  • Prepare for administrative site visits by NCI staff members;
  • Take advantage of collaboration with other NCI initiatives and programs as appropriate.

The following additional responsibilities will also apply for each DRSC awardee:

  • Each DRSC will be subject to periodic performance evaluation coordinated by the NCI--DRSC awardees will be expected to participate in these evaluations;
  • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies;
  • All institutions/organizations participating in a given DRSC will be expected to share program knowledge, specimens, data, research materials, and any other resources necessary and relevant to the award.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The designated NCI Program staff members will have substantial involvement as Project Scientists in the awards under this FOA. The specific roles of the substantially involved NCI staff members include the following activities:

  • Serving as the NCI lead project scientists and voting members of the DRSC Steering Committee;
  • Assisting in avoiding unwarranted duplications of effort across the DRSC program;
  • Monitoring the operations of the DRSC and making recommendations on overall project directions and allocations of funds;
  • Reviewing the progress of individual DSRC and their specific shared activities;
  • Participating in the development and evaluation of cross-DRSC projects;
  • Assisting the DRSC awardees as a liaison in stimulating their broader interactions with other NCI and NIH programs to disseminate results and outcomes and effectively leverage existing NIH/NCI resources and infrastructures;
  • Evaluating the adherence of DRSC awardees to the approved resource sharing plan.

Areas of Joint Responsibilities include:

The NCI will establish a Drug Resistance and Sensitivity Center Steering Committee (DRSC-SC) to coordinate the activities of the five DRSC sites. The DRSC-SC will promote, in collaboration with DCTD (Division of Cancer Treatment and Diagnosis) and DCB (Division of Cancer Biology) staff members, the exchange of scientific findings and potential collaborations between the investigator teams and NCI intramural laboratories. 

The DRSC-SC will be composed of the PD(s)/PI(s) of each DRSC and five members of the Drug Resistance Working Group composed of DCTD and DCB program staff members.  Other NCI investigators and/or external drug resistance experts who are not affiliated with DSRC network may also be invited to participate, for example if additional expertise is needed. 

Formal meetings of the DRSC-SC, including invited outside experts and interested Experimental Therapeutics Clinical Trials Network (ETCTN) investigators will be held twice each year, with at least one of these meetings being a face-to-face meeting at the NCI. 

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)

Telephone: 301-710-0267

Scientific/Research Contact(s)

For inquiries regarding cancer pharmacology and drug development:

L. Austin Doyle, M.D
National Cancer Institute (NCI)
Telephone: 240-276-6565
Email: doylela@mail.nih.gov

For inquiries regarding cancer biology:

Shannon K. Hughes, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6224
Email: shannon.hughes@nih.gov

Peer Review Contact(s)

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Financial/Grants Management Contact(s)

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

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